Characterization of prenatal healthcare for implementation of congenital toxoplasmosis surveillance program: cross-sectional study

ABSTRACT BACKGROUND: Prenatal toxoplasmosis remains a neglected disease worldwide and few government programs focusing on its prevention are available. Success in these programs has been extensively reported in the literature, yet the strategies used for their implementation, as a model for such actions in different communities, have not been described. OBJECTIVE: To describe the aspects of prenatal care strategies in 13 municipalities within the regional healthcare unit of Araçatuba, in the northwestern region of the state of São Paulo in 2017, focusing on congenital toxoplasmosis. DESIGN AND SETTING: Descriptive study on prenatal healthcare within the Brazilian National Health System, in 13 participating municipalities. METHODS: Data on serological tests, referral clinics, notifications, healthcare strategies, health education and drugs for infected children were requested through a questionnaire that was sent via e-mail to people responsible for healthcare services in these municipalities. RESULTS: Major differences relating to diagnoses, reference outpatient clinics, notifications, health education and healthcare and drugs for infected children were reported among the prenatal strategies of these 13 municipal healthcare services. CONCLUSION: The lack of standardized prenatal strategy in the study area may compromise the prevention of infection. However, our identification of each aspect of prenatal care corroborates the need to implement a healthcare surveillance program relating to congenital toxoplasmosis.

newborns up to one year of age, has been observed. 7 In Switzerland, three decades of serological monitoring of pregnant women led to an 85% reduction in the incidence of congenital toxoplasmosis. 8 Similar results have been found in other countries such as France 9 and Austria. 10 Technical and scientific standards for promotion, protection and recovery of health have been developed within the Brazilian National Health System (Sistema Único de Saúde, SUS). SUS has the mission of promoting public health actions to ensure conditions of physical, mental and social wellbeing for the entire population. This is implemented by the Brazilian Ministry of Health and by the state and municipal health departments, through socioeconomic policies aimed at diminishing the risks of diseases, in a hierarchical flow. 11 Hence, Brazilian states have adopted policies consisting of preventive strategies against congenital toxoplasmosis, with protocols for diagnosis, attendance and treatment among mothers and children, at public healthcare services. 12

OBJECTIVE
Through this study, we aimed to describe the aspects of prenatal care strategies in 13 municipalities within the regional healthcare unit of Araçatuba, in the northwestern region of the state of São Paulo in 2017. We focused on congenital toxoplasmosis and ascertained the possibility of implementing a surveillance program for congenital toxoplasmosis in this regional healthcare unit. inhabitants. These municipalities are grouped into three regional management board groups, namely: "Central, " "dos Lagos, " and "dos Consórcios".

In
All municipal healthcare managers present at the board meetings of the Regional Inter-Agency Committee (Comissão Intergestora Regional, CIR) were invited to participate in the project, which had the aim of improving the healthcare provided for pregnant women with congenital toxoplasmosis, through academic-scientific partnerships between epidemiological surveillance bodies and municipal health departments.
Among the municipal managers who agreed to participate, some information was requested through a questionnaire that was sent out via e-mail to each municipal health department. The data recorded were grouped in terms of the following general characteristics: infrastructure available in the municipalities for prenatal care and for making the serological diagnosis; the time at which trimestral screening was performed and the parameters adopted for this; and the confirmatory test and the place and circumstances used for notification of the infection ( Table 1); and also according to the drug intervention ( Table 2).
Information from each municipality was described individually and differences between strategies were recorded.
The manual "Gestational and congenital toxoplasmosis: health surveillance, diagnosis, treatment and conduct", which was created in the city of Londrina, Paraná, in 2006, was used as reference material. This material was then implemented in the state of Paraná as part of the program "Paraná-born Mothers -Books for healthcare provided for combating prenatal toxoplasmosis". 15 The study "Implementation of the healthcare surveillance program for congenital toxoplasmosis in the northwestern region of the state of São Paulo" was approved by the local research ethics committee on April 27, 2018 (opinion report no. 2,625,140).

RESULTS
Out of the 40 municipalities that form the regional healthcare unit of Araçatuba, 13 agreed to participate in this project. In  Classification of pregnant women at risk of congenital toxoplasmosis, based on the serological results, is not carried out in one municipality; and in two there was no answer regarding this question. Concerning the criteria used to make the notification, the answer was "after confirming the infection" in 9/13 municipalities, while there was no response from one and the answer from two was incomplete, since it was stated that notification was only performed in cases in which the pregnancy was not more than 16 weeks.
Therapeutic intervention was inadequate in all the municipalities. According to the responses, it was implemented "after medical prescription, " "after serological result" or "as soon as possible" in 8/13 municipalities. In the others, it was done after waiting for the result from the avidity test. Spiramycin was reported to be the active substance of choice by 12/13 municipalities.
In only 2/13 municipalities, the pregnant woman is reevalu-   The presence of members of the community in these teams, such as community health agents (agentes comunitários de saúde, ACS), facilitates creation of bonds with the population and interactions with the team of healthcare professionals. 18 Thus, indirectly, this assists in health education and in actively seeking out pregnant women to ensure that they receive complete prenatal follow-up. Incorporation of veterinarians and graduates in epidemiology, public health, zoonoses and food inspection, among others, in NASF teams is highly recommended, in order to add quality to the dissemination of knowledge to the population. Successful work by veterinarians has been reported in relation both to prevention of zoonoses 19,20 and to responsible conduct towards companion animals. 19 It is paramount that women understand the T.
gondii cycle and its transmission routes, in order to avoid infection during pregnancy. 21 In the states of Rio de Janeiro and Paraná, lack of knowledge about toxoplasmosis was observed among, respectively, 232/405 (57.28%) and 177/330 (53.63%) pregnant women attended through the municipal public healthcare network. 22 In a city in the northwest- Early diagnosis is crucial for preventing congenital infection.
Some aspects of how laboratory tests are organized, such as daily test production capacity and the sample collection site, can reduce the time taken to detect acute infection.
There is a lack of specific guidance from the Brazilian Ministry of Health regarding the place at which blood collection should be performed, for investigating the presence of anti-T. gondii antibodies.
Nonetheless, shortening the time taken to implement therapeutic intervention after pregnant women become infected is crucial for reducing the damage to fetuses. 24 In the state of Minas Gerais, Brazil, all blood samples from pregnant women are collected on filter paper and are sent to the reference laboratory within 24 hours, using a specialist postal service for transporting this material. The result is made available online, with consequent release of the therapeutic drug through SUS, if necessary. This highly organized system in Minas Gerais shows that, regardless of the place at which blood samples are collected, efforts should be concentrated on implementation of a flow process for transportation of samples, so as to optimize the time that elapses between blood collection and drug interaction.
Diagnostic screening for gestational toxoplasmosis, which is recommended at the beginning of each gestational trimester, was the matter of greatest divergence from the guidelines. This was not incorporated within the healthcare strategy of any of the municipalities in our research.
Infections in the last trimester cause mental disorders and hearing impairments that are often manifested after birth. 25,26 This late diagnosis may be related to negligent evaluation in the third trimester.
However, since the rate of vertical transmission of T. gondii increases with increasing gestational age, trimestral serological evaluation, at least, is essential within surveillance programs for congenital toxoplasmosis. 9 Clinical patterns of asymptomatic acute infection, which may occur at any stage of pregnancy, can only be demonstrated through serological monitoring. Detection of these cases increases the chances that the baby will grow without after-effects, since it triggers a flow of actions for early and continuing treatment during pregnancy and after birth. Moreover, the costs of treatment of the disease due to infection at the end of pregnancy may be higher than the costs of serological monitoring within prenatal care. Such situations may have an impact on a country's economy. This was seen in Austria, where the government was able to save 258 million euros over a 17-year period through bimonthly serological evaluations on pregnant women. These evaluations reduced the extent of damage caused by congenital toxoplasmosis. 10 The diagnostic methodology needs to include quantification of antibodies in order to aggregate information that can guide the medical conduct until acute infection has been confirmed through laboratory data. By making this quantitative information available, antibody curves for paired samples over 15-day intervals can be determined. This aids in interpreting the results from IgM-reactive individuals. Another way to confirm infection is to use an IgG avidity test on samples that were positive for IgM in screening tests. 14 To make this diagnosis, it is essential to define a flowchart for confirming recent infections. IgG avidity tests should be requested within the first 16 weeks of pregnancy, if the pregnant woman is positive for IgG and IgM in the screening test. To achieve this, urgency in temporal dynamics between conducting tests on samples and beginning the treatment for congenital toxoplasmosis is required.
Thus, we suggest that in the cases of the two municipalities, in which the reports are received only 20 days after the samples were collected, alternatives need be discussed with the aim of shortening these temporal dynamics. The healthcare managers responsible for prenatal care should advise the laboratory service to perform the avidity confirmatory test on the same sample as used for screening.
In this proposal for a program for preventing toxoplasmosis, efforts need to be made to facilitate drug interventions in urgent cases of gestational toxoplasmosis. To do so, it is paramount to define a strategic flowchart with diagnostic actions that go from taking samples from pregnant women to production of the diagnostic report that is to be given to the doctor responsible for the prenatal care. 13 Prenatal care in the municipalities surveyed was unsatisfactory.
Moreover, there was a need to change the number of ultrasounds performed, in order to achieve bimonthly monitoring, and monthly monitoring in cases in which changes to the fetus are observed.
Through ultrasounds, conditions such as ventriculomegaly, higher hepatosplenic or periventricular density, focal injuries to the brain tissue, calcification, punctate lesions, fetal ascites or greater placental thickness can be ascertained. 27 In Brazil, compulsory notification for gestational toxoplasmosis has only been established in sentinel units. These units are used in Brazil to improve the notification of diseases without any use of a specific questionnaire for epidemiological investigation. Thus, it might be possible to aim towards a better notification service for acute toxoplasmosis if no sentinel units are available.
Classification of the risk of congenital toxoplasmosis and the criteria for notification need to be intensified. This is especially important after two-thirds of pregnancy has passed. This is the point at which the greatest lack of monitoring has been reported.
This lack of monitoring may be due either to lack of prenatal follow-up on the part of pregnant women, or to lack of requests for serological tests at this time, which was reported in several municipalities. The recommendation given in the program is that detection of IgG and IgM-reactive samples with low IgG avidity should be notified until the 16 th gestational week, and that seroconversion of IgG and IgM when IgG and IgM are reactive should be notified at any time during prenatal care. 15 The level or quality of therapeutic intervention reflects the success of newborn recovery and damage reduction. 14 In 84.6% of the municipalities, the quality of therapeutic intervention was insufficient, especially regarding the adequacy of active substances that were administered after confirmation of acute gestational toxoplasmosis, but also concerning immediate availability of spiramycin and the time between blood collection and the beginning of the treatment.
Use of spiramycin in gestational toxoplasmosis protects the fetus from ocular damage, as observed in a cohort study conducted in Colombia. In that study, ocular toxoplasmosis was found in 1/15 children (6.6%) from pregnant women who used spiramycin, whereas it was found in 5/8 babies (62.5%) from untreated pregnant women, and in two of these cases, involvement of the central nervous system was verified. 28 In a cohort study conducted in Goiânia (GO), Brazil, congenital infection was detected in 58.33% of newborn babies from pregnant women who received treatment with spiramycin, and in 18.6% of them the damage was severe. On the other hand, among untreated pregnant women, infection was found in 73.04% of their babies, with severe damage to health in 60.7% of them. 4 In treating gestational toxoplasmosis to avoid congenital toxoplasmosis spiramycin needs to be added. This acts as a parasitostatic agent on the placental barrier. Sulfadiazine and pyrimethamine antiparasitics are added to act on fetal tissues.
Folinic acid needs to be administered whenever its antagonist, pyrimethamine, is activated. 15 Through the instrument used, we were able to see that actions

CONCLUSION
It needs to be acknowledged that the methodology used in the present study, i.e. interpretation of data collected via email, may have led to some bias. However, to the best of the authors' knowledge, no guidelines on how to start a preventive program for gestational and congenital toxoplasmosis currently exist. Therefore, the simple investigative methodology presented here can be used in other locations as the first stage in implementing a preventive program for combating gestational and congenital toxoplasmosis.
We observed differences in the prenatal strategies among the municipalities surveyed. However, the differences in strategies that were detected confirm that there is a need to implement a healthcare surveillance program for congenital toxoplasmosis.